Use of DNA in Identification
The following is an excerpt from a talk given by
Dr. Eric S. Lander at the "Winding Your Way through DNA" symposium,
which took place at the University of California San Francisco in
1992. At the time he gave this talk, Dr. Lander was a professor in
the Department of Biology at MIT and the Director of the MIT Center
for Genome Research.)
Excerpted from the symposium
transcripts with permission of the University of California, San
In the introduction to Dr. Lander's talk, he refers to the variations
in DNA coding among human beings. . . .
Dr. Lander: How much spelling difference is there?
Well, there is almost complete identity between any two human beings.
Look at the neighbor to your left and to your right. You're 99.9%
identical. That should make you feel very common, part of a common
species. But of course, in a genome of three billion letters, even a
tenth of a percent difference translates into three million separate
spelling differences. And so I invite you again to look to the left
and look to the right and notice how unique you are. There is no one
in this audience who has the same DNA sequence as anyone else.
And indeed, your DNA sequence is unique amongst all DNA sequences of
any human that has ever lived and will live for quite some time to
come. Unless you have an identical twin, in which case you do have
someone who has the same DNA sequence. But apart from that, your DNA
sequence is yours and yours alone. Should you choose to leave your
DNA sequence behind here in some form in some biological tissue, in
principle, I ought to be able to look at it and by its uniqueness know
whose it is.
Thus is born the notion of DNA identification. And it was quickly
realized that this DNA identification would be especially useful in
legal cases, in the criminal courts. Of course, law enforcement
officials over the course of many years have looked for things that
uniquely identify individuals, so as to find evidence that links a
criminal to the scene of a crime. In fact, 1992 was the 100th
anniversary of the use of fingerprints as an identifier.
They're uniquely powerful. They are essentially unique, and there are
computer databases for fingerprints that are online across the country
and are used. They're great, except that for many crimes, no
fingerprints are left behind. A very common example, and an important
example, is rape. For property crimes you may find fingerprints, but
for many violent crimes it's harder sometimes to find fingerprints.
So scientists look for other markers, biological markers, for example,
as you might find in a semen sample from a rape. There has been
success looking for protein differences, cell surface differences,
things like the HLA complex and blood groups. But in fact, the
variation is nowhere near as spectacular as in fingerprints - that is,
until it was possible to read DNA.
DNA gives us rich results, and just as detailed as a fingerprint, in
principle. You might think what we do is to take a sample and just
read out a DNA text in its entirety. It would be a wonderful thing if
we could get that from a sample, but that is the business of the
Human Genome Project,
not the business of the local constabulary yet. So
when we do DNA comparisons, we can't read all three billion letters.
What is done instead is that a very small handful of sites of
variation are examined. Sites of variation here on this chromosome,
perhaps, or one here, or one here, and one picks enough sites of
variation to be able to have enough markers of difference.
At least in the forensic applications commonly done today, people
don't actually read out the sequence. For economic reasons, for being
able to do this more quickly and more cheaply, they look instead at
regions that have spelling differences that are due to repetitions of
some sequence. There are repeat sequences all over the genome and, in
any particular region, let's pretend this is chromosome #1, you may
have three copies. I might have four copies, someone else five
copies, someone else one copy - typically, an unimportant repeat that
has no biological function, but we all might differ.
By taking that DNA and cutting it with an enzyme that recognizes a
distinctive site here, running it out by electrophoresis to be able to
separate these fragments by size, and probing it with a piece of
radioactive DNA from this region, one can visualize bands
corresponding to the lengths of these fragments. And each of these
different chromosome configurations, each of these different spellings
due to different numbers of repeats, can be visualized as
different-sized bands on a ladder, much like a bar code. And so a
forensics scientist, examining an evidence sample E here, might probe
it first with Probe #1 for the first site of variation and see the
pattern. Then he or she might probe it for the next site, the next
site, and the next site, and compare it to the DNA patterns taken from
two suspects, Suspect #1 and Suspect #2.
If Suspect #1 has a different DNA pattern than the evidence, the
suspect is excluded from having committed - well, more exactly - from
having left this evidence. It's another question of how the evidence
relates to the crime. But that evidence sample of DNA cannot possibly
be Suspect #1's.
Suspect #2's DNA corresponds perfectly at each of the four places of
variation on the human chromosomes examined. Does this mean that
Suspect #2 is indeed the person who left that evidence sample? What
does it mean, to say Suspect #2 is included amongst those who left it?
Of course, to know how strongly we should take this evidence, we need
to know how rare that pattern would be - if it's a question of
population genetics - and for that purpose databases have been
assembled of how frequent these patterns are in the population. These
are tricky questions, and we'll return to them very briefly.
Those are simply the ideas underlying DNA fingerprinting, as it's
popularly called, or DNA typing
or DNA identification,
as we prefer to
call it. Within five years of the notion of DNA spelling differences
being used for medical purposes, there were already private companies,
Selmar, Lifecodes, and others, which grew up to provide DNA typing
services to law enforcement officials, and by 1989 the FBI had its own
DNA typing lab in the Hoover Building in Washington. There were
dramatic ads in the appropriate press, such as this one here from
Selmar (showing ad).
"DNA Fingerprinting Links the Criminal to the Crime," with the handcuffs here being a double helix.
For the most part, this has been a dramatic and broad success.
Increasingly, in rape cases, there is no need for a victim to testify
about whether a sexual act took place. There's no question,
typically, about mistaken identity being the problem, because DNA from
a semen sample can be used to link a suspect to that semen sample. In
fact, it has been useful for excluding innocent people. The FBI says
that, of many test results, that they could never exclude with
standard blood markers, nearly a third of those people are exonerated
immediately upon DNA testing. Many rapists, because of this, now
In essence, DNA evidence is rapidly becoming, in principle, an
irrefutable proof of identification. But of course, nothing is ever
so simple. Scientists are a demanding lot, a skeptical lot, a
rigorous lot. It's not enough to say it's okay in principle - it must
be okay in practice as well. And although everyone agrees that this
is a spectacular technology, controversies have erupted in the
scientific community from time to time over whether it's really being
done right. Fights erupt over DNA fingerprinting
because it's such an important technology.
What have these fights been about? They have not been about how to do
it in principle. They have been about how to do it in practice, and
how well-regulated the practice is. For example,
DNA fingerprints should look like bar codes. (Showing a slide) Here is a not-very-good
example of a DNA fingerprint,
which was used in a criminal case in New
York. It's one I know well, because it was one where I was asked to
serve as an expert witness, which is how, from my medical genetics
background, I got deeply involved in this.
It was an interesting case, because it showed what scientists can do
when they put their heads together. Halfway through this case, when
all the evidence was being considered, all the scientists who had
testified as witnesses for the prosecution, and all the scientists who
had testified for the defense, met outside the courtroom without the
lawyers present and talked about the evidence. And at the end of the
day we agreed the evidence was terrible, and we went back to court
with a joint statement for the witnesses on both sides, saying the
evidence was no good. It was the first case in which
DNA fingerprinting was
actually thrown out because of the way it was
practiced. It was also an example, I think, to the legal community,
that scientists are not necessarily hired guns to say whatever you
tell them to say.
The other controversy that has arisen is about how to interpret a
match. What frequency should you put on it? How rare is a pattern?
How odd is a match? And for this, the controversy is a technical one
and a complex one, but it has to do with the fact that the frequency
of the different DNA patterns of different genes vary across the
population. This is actually a blood group frequency distribution.
Similar things are known for other types of DNA differences. And so
there has been active controversy about exactly what weight we should
put on samples. Are the odds being quoted one hundred-fold too high?
Are they exactly right? Maybe they're one thousand-fold too high.
Scientists are arguing actively about this.
There is a good mechanism in the scientific community for focusing on
such arguments. It is the National Research Council Committee from
the National Academy of Sciences. For my own sins in that New York
case, I served on this Committee for a period of three years, which
finally culminated in the production, after a very, very long
gestation, of an NRC report called, "DNA Technology in Forensic
The really important thing the committee has done is calling for
defined standards for laboratory work. For new standards of
statistical calculations. And most importantly to my mind, it called
for a mandatory proficiency test - that the laboratories that are
doing this work should be subjected regularly to blind proficiency
testing, to insure that they did the work well on a regular basis. It
is in some sense appalling that there are no mandatory standards for
something as important as forensic testing. There are higher
standards, indeed for the laboratory practices of someone who will
diagnose strep throat than for the laboratory practice of someone who
will create a DNA fingerprint
that could be used to send someone to Death Row.
Another point to mention is databases. There has been discussion
about creating national databases of everyone's DNA type. That way,
when a rape is committed, there's no need to find a suspect. You take
the segment sample and get its DNA pattern, and compare it to a
database of everyone's DNA pattern and find out whose it was. There
are many people who feel understandably uncomfortable about such a
national database. So legislatures have instead decided in some
states to set these up, not for all citizens, but for only those
convicted of, say, sex offenses, and other states for those convicted
of any felony.
There is a lively controversy over what sorts of databases should be
set up and there are those who say - why should it matter? Why should
you care if you're in a database? After all, if you're innocent,
there's no chance the technology will do you any harm. Well, even if
standards are being discussed and looked at, and I'm an optimist, I
feel that the standards are being worked out well. I think the
Academy's report and many other steps are doing a great job of putting
this on the most rigorous footing possible.
is a marvelous technology to amplify DNA. It allows you to take a
specific region of DNA on the chromosome, and by using little black
primers here and copying back and forth, back and forth, just the
particular region you want to copy, making two, then four, then eight,
then sixteen, up to millions of copies of a particular region, and so
in principle it is possible to start from the DNA of a single cell and
get enough DNA to analyze it. That makes it possible not just to
analyze blood stains of the sort that were seen before in which you
could get one microgram, one millionth of a microgram of DNA, or semen
swabs from a rape, some of which give you enough to analyze by
standard techniques, but in fact even shed hair has enough DNA at its
root. A urine sample, saliva sample, will have enough DNA in most
cases. It's possible that by licking an envelope you deposit enough
DNA to trace from the seal of the envelope.
Obviously, a technology that is so powerful and that is that sensitive
must be used even more carefully, since you can imagine that if I
sneeze on something, my DNA is there, too. And so there is tremendous
need to avoid contamination. Whether laboratory practice is up to
that - the proficiency tests have to be put in place to guarantee that
they're up to that. These are questions under debate.
Let me shift gears . . . .
In 1975, the military in Argentina overthrew the government of Isabel
Peron, and this was a very rigid ideological military. It was a
military which said such things as the following quote from the
military governor of Buenos Aires, a direct quote from a speech to the
public: "First, we will kill all the subversives, then we will kill
their collaborators, then their sympathizers, then those who remain
indifferent, and finally, we will kill the timid."
They had a lot of enemies indeed (showing a slide) as shown in this
"tree of subversion." This is all the subversive groups, based on a
similar drawing that was made in Germany for the SS during the Nazi
I note for you just briefly, because I can't read everything, the
roots of the tree of subversion are Marxism, Zionism, and Free
Masonry. But other important branches include the liberals,
evangelicals, the Anglicans, and the Rotary Club. It's on there.
The military junta set out in a systematic fashion to eradicate the
opposition and to terrorize society, and did so with sweeps through
neighborhoods, picking up subversives and non-subversives, rather
indiscriminately, taking whole families at times, young families.
Many people disappeared, and no one knew because of the lack of
coverage, the actual scope of what was going on. They only knew their
own children had disappeared.
Eventually, after the fall of the government, the Commission on the
Disappearances of Persons found 9,000 documented cases of
disappearances. Correcting for underreporting and the lack of
documentation, it's estimated that about 15,000 persons were
"disappeared." Well, as these cases began to build up, older women,
grandmothers, typically, of young men and women in their 20s and 30s
began to get together in the main square, the Placo de Mayo in Buenos
Aires, and began to talk, as support groups for one another, looking
for their lost children. They began to talk, and they began to march,
and they began to protest.
And as they protested, people came to the square and shared with them
stories and the stories said, we've heard of cases of children
appearing in military families that were previously childless, and the
wife wasn't pregnant. They would occasionally have stories from
people released from prison saying that their friend had been seen
alive in prison and had given birth. Midwives and obstetricians were
at times kidnapped and blindfolded from the streets of Buenos Aires,
taken to military prisons, forced to help in the delivery of children,
then blindfolded and put back on the streets. Sometimes during the
delivery, a woman might say to such a midwife or obstetrician, "My
name is so-and-so. Please tell my mother." And in once case that has
been documented, the midwife did this favor, and she was later killed
Phony birth certificates began showing up at the schools a few years
later, and registrars quietly told the grandmothers at the Placo de
Mayo - or told someone who told the grandmothers - and the
grandmothers took notes. By 1983, when the Falklands war led to the
fall of the military junta, the grandmothers contacted the AAAS, the
American Association for the Advancement of Science, and asked for
help in identifying and proving that these were their children, and
they demanded that genetics be used to do it. They got in touch with
Mary Clair King, a professor at the University of California Berkeley
- a true hero to me - a friend and colleague, whose work I am
Mary Claire King went and worked with the grandmothers of the Placo de
Mayo to begin, as they say, "searching for two generations." She
began to try to get court orders for some of the children taken into
military families, to do some sort of genetic typing and show that,
indeed, they belonged to these biological grandparents, rather than to
the alleged adoptive parents.
Originally, simple HLA typing was used, typing of cell surface
markers, but this was not terribly powerful in these cases. DNA
fingerprinting of the sort I described before was used, but for
technical reasons I won't go into, was not as powerful. More
powerful, unique sequences of DNA would be needed. And so Dr. King's
group turned to looking at a particular bit of DNA called the
mitochondria DNA. It exists in a little organelle - a little package
outside the nucleus of the cell. It's a small bit of DNA, and what's
important about it is that you get it from your mother. It's only
passed on in the egg, not the sperm. And so mom passes it on to all
her kids and every female passes it on to all of her kids. If I can
read snippets of unique, variable sequence mitochondrial DNA, I can
trace maternal lineage.
(Showing a slide)
The older woman at the top is Heidi Llemos, and these are two of her
grandchildren. She and her adult daughter and her son-in-law were all
kidnapped by the military. She was tortured and eventually released.
Her adult daughter and her son-in-law were eventually killed. But the
daughter was two months pregnant when she was picked up, and a
prisoner told Heidi that her daughter had been kept alive and had
given birth in prison.
Heidi spent ten years looking for that grandchild of hers. She
eventually found a child living with a woman who had been the military
guard in charge of female prisoners at the prison and, it was quite
plausible that this child was her daughter's, and she demanded that
the courts do DNA testing. Mitochondrial DNA sequences were obtained
under court order, and were found to match perfectly between this girl
and Heidi. She went to court and demanded the return of the
The military family made the argument, "How can you return this
grandchild to a family she's never known?" claiming it wasn't in the
child's best interests. The girl didn't even know Heidi Llemos. The
grandmothers of the Placo de Mayo said that when the society knows
that these people murdered her parents, how can you not release her,
because when she becomes an adult she'll find out. Is it worse to
move families now, or to find out when she's an adult that she's been
raised all of her life by her parents' murderers? The Supreme Court
of Argentina agreed. . . . . Overall, about 51 living children have
been identified, and most of these have been restored to their natural
Let me also mention to you two other applications of
technology. It turns out to be useful in identifying
not only humans, but plants as well. One of the great uses of
turns out not just to be in the criminal courts but in
the civil courts - for corn and tomato cases. People spend a
tremendous amount of time developing strains of corn by old breeding
techniques, and they can never gain intellectual property protection
for it, never get patent protection on it, because there's no way to
prove this corn plant was theirs. So they put all this work into
developing the strain, and someone steals the strain, and they can't
prove anything about it. Well in fact, now you can do
DNA fingerprinting on corn plants, and many large seed companies routinely
maintain databases of the DNA fingerprints
of all their important
varieties, so they can go to court and prove their ownership. It
creates economic protection, and it gives people an incentive to
And then, very briefly, the ultimate in DNA paternity testing. As I
was getting on the plane yesterday to come here, I found in the New
York Times a story about DNA taken from a 40-million-year-old termite,
preserved in amber. And DNA sequencing by PCR has been done on this
termite to answer questions about who is the parent of the modern-day
cockroach - was it really the termite? They are comparing and finding
all sorts of novel things out as to whether the termite really was or
wasn't the evolutionary ancestor of the cockroach. Indeed, if we take
DNA paternity testing way back, it brings us to our common origins as
a species, and to the common unity of life.
Basic science. It leads us in unexpected directions that have social
consequences. No one sets out to develop
DNA identification, the
looking at DNA spelling differences for the purpose of criminology
applications. The research was driven by a whole different set of
challenges and questions, and yet the capability to read and interpret
DNA spelling differences has had consequences in all of these areas.
As a society, we can be pleased and proud that our technology, that
our science, has had social applications, but what we must do together
as scientists and as a society is to make sure that we apply these
technologies with the highest of standards. We must strive to apply
them - as with Argentina - to the highest of purposes.